Migraine affects 12% of the world population. Chronic migraine, which completely disrupts the lives of sufferers, affects close to 3%, and is extremely difficult to treat. Arguably the highest priority in migraine research is the development of new drugs, yet not a single drug has been developed specifically for the prevention of migraine. Fortunately, migraine models have made significant advances in recent years, and new systems neuroscience tools have opened up possibilities for further work. This proposal attempts to maximize the benefits of existing migraine models, increasing throughput and reliability both in vitro and in vivo, so that standardized testing can take place. We will use an optically-based multi-animal platform to increase the throughput and data-richness of the cortical spreading depression (CSD) model in vivo. We will validate this model against our prior results as well as those of an experienced CSD researcher at another institution. We will also use the nitroglycerin model of migraine without aura to complement the CSD model, which is most relevant to migraine with aura. Finally, we will deploy a high-throughput brain slice model of CSD, made possible by novel microfluidic devices we have developed with our collaborators. We will test the model with an array of compounds known to be active (and inactive) in CSD and migraine. Overall, our proposal should significantly advance efforts to develop new migraine treatments, by providing modular, immediately usable screening tests for migraine drugs.